Language
English
Publication Date
4-8-2026
Journal
bioRxiv
DOI
10.64898/2026.04.06.716309
PMID
41993385
PMCID
PMC13082029
PubMedCentral® Posted Date
4-8-2026
PubMedCentral® Full Text Version
Post-print
Abstract
Viral infection polarizes monocyte-derived dendritic cells (moDC) to initiate type 1 immunity. The availability of overlapping (homologous) MHC class I and II epitopes, an occurrence frequently and primarily associated with intracellular infection, significantly enhances this process; however, the underlying mechanism(s) are unclear. We demonstrate that moDC loaded with homologous MHC epitopes acquire a cDC1-like phenotype in a process governed by mTORC1. mTORC1 pathway inhibition leads to NF-κB-mediated expression of IL-12 and other type I immune polarizing genes. The observed cDC1-like gene signature was also significantly enhanced in clinical moDC vaccine products made through methodologies that enforced class I and II antigenic homology. Collectively, these findings reveal a novel and previously unrecognized mechanism of immune governance that might also be exploited in cancer immunotherapy.
Keywords
Type 1 conventional dendritic cell, monocyte-derived dendritic cell, major histocompatibility complex, immune regulation, cancer immunotherapy, Type 1 immunity
Published Open-Access
yes
Recommended Citation
Amanya, S B; Murthy, A; Bisht, N; et al., "Overlapping MHC class I/II Epitopes Program cDC1-like Differentiation of Monocyte-Derived Dendritic Cells via mTORC1 Signaling Inhibition" (2026). Faculty, Staff and Students Publications. 7999.
https://digitalcommons.library.tmc.edu/baylor_docs/7999
Graphical Abstract